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Now that I have collected the necessary information, I'll provide a comprehensive review of the GO-CAM model with ID 632cf60a00000788.

Review of GO-CAM Model: gomodel:632cf60a00000788

Basic Model Information

  • ID: gomodel:632cf60a00000788
  • Title: USP20-mediated STING deubiquitination leading to STING stabilisation (Human)
  • Taxon: Human (NCBITaxon:9606)
  • Status: Production
  • Comments: "Automated change 2023-03-16: RO:0002213 replaced by RO:0002629"

Model Overview

This GO-CAM model represents the molecular mechanism by which USP20 (with the assistance of USP18) deubiquitinates STING/MITA, leading to STING stabilization and promotion of antiviral innate immune responses in humans. The model contains three main molecular activities and their causal relationships.

Entities and Their Functions

1. USP18 (UniProtKB:Q9UMW8)

  • Function: Molecular adaptor activity (GO:0060090)
  • Location: Cytoplasm (GO:0005737)
  • Process: Antiviral innate immune response (GO:0140374)
  • Evidence: Direct assay evidence (ECO:0000314) from PMID:27801882
  • Causal relationship: Directly positively regulates USP20's deubiquitinase activity

USP18 is correctly annotated as having a molecular adaptor activity, which is consistent with the literature showing it functions as a non-enzymatic adaptor that recruits USP20 to STING.

2. USP20 (UniProtKB:Q9Y2K6)

  • Function: Cysteine-type deubiquitinase activity (GO:0004843)
  • Location: Cytoplasm (GO:0005737)
  • Process: Antiviral innate immune response (GO:0140374)
  • Evidence: Direct assay evidence (ECO:0000314) from PMID:19424180
  • Causal relationship: Directly positively regulates STING's cyclic GMP-AMP binding

USP20 is correctly annotated with deubiquitinase activity, which is responsible for removing K48-linked ubiquitin chains from STING.

3. STING1 (UniProtKB:Q86WV6)

  • Function: 2',3'-cyclic GMP-AMP binding (GO:0061507)
  • Location: Endoplasmic reticulum membrane (GO:0005789)
  • Process: Antiviral innate immune response (GO:0140374)
  • Evidence: Direct assay evidence (ECO:0000314) from PMID:23747010

STING1 is correctly annotated as having cyclic GMP-AMP binding activity, which is a key function in DNA-sensing pathways.

Evaluation of the Model

Strengths

  1. Accurate representation of biological process: The model correctly depicts the USP18-USP20-STING relationship described in the literature. USP18 functions as an adaptor to recruit USP20, which then deubiquitinates and stabilizes STING.

  2. Appropriate evidence citations: Each activity and relationship is supported by appropriate published evidence with direct assay evidence codes.

  3. Correct subcellular locations: The subcellular locations for the proteins are correctly annotated based on the literature.

  4. Correct causal relationships: The model uses the appropriate causal predicate RO:0002629 (directly positively regulates) to represent the activating relationship between USP18 and USP20, and between USP20 and STING1.

Issues and Recommendations

  1. Missing K48-linked ubiquitination details: The model does not explicitly indicate that USP20 removes K48-linked ubiquitin chains from STING, which is a key mechanistic detail from the Zhang et al. (2016) paper. Consider adding this specificity to the annotation.

  2. Missing representation of STING stabilization outcome: While the model shows that USP20 activity positively regulates STING, it doesn't explicitly represent the stabilization of STING protein levels as an outcome. Consider adding an annotation to represent this functional consequence.

  3. Potential redundancy in causal associations: USP20 has two identical causal associations to STING1 (identical predicate and target), which appears to be redundant and should be consolidated into a single relationship.

  4. Missing functional consequence of STING activity: The model could be expanded to show what happens downstream of STING activation - specifically the induction of type I interferons and proinflammatory cytokines as described in the literature.

  5. Complex representation considerations: According to GO-CAM best practices for annotating complexes, since USP18-USP20 function together but have distinct activities, they are correctly represented as separate entities. However, the model could more clearly represent their physical interaction.

Consistency with Literature

The model is largely consistent with the findings reported in the key references:

  • Zhang et al. (2016) showed that USP18 functions as an adaptor to recruit USP20 to deubiquitinate STING in a manner independent of USP18's enzymatic activity.
  • The model captures the essential relationship that USP20 deubiquitinates STING, leading to STING stabilization.
  • The function of STING in binding cyclic dinucleotides like 2',3'-cGAMP is accurately represented.

Summary and Conclusion

The GO-CAM model gomodel:632cf60a00000788 provides a good representation of the USP18-USP20-STING pathway in antiviral innate immune responses. It accurately captures the key molecular activities and their causal relationships. The model uses appropriate GO terms, evidence codes, and citations.

To improve the model, I recommend: 1. Adding explicit annotation of K48-linked deubiquitination 2. Including the stabilization of STING protein levels as an outcome 3. Resolving the redundant causal association from USP20 to STING1 4. Extending the model to include downstream activation of IRF3/NF-κB and type I interferon production 5. More clearly representing the physical interaction between USP18 and USP20

Overall, this is a well-constructed model that effectively captures the key aspects of USP20-mediated STING deubiquitination in antiviral immune responses.